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Question: Who is the ideal patient to start on exenatide?
Answer: Exenatide (Byetta, Amylin/Lilly), a newer therapy option for patients with type 2 diabetes, has gained impressive popularity among prescribers. It works as an incretin mimetic, effectively replacing glucagon-like peptide 1 (GLP-1), thereby increasing early satiety, reducing glucagon levels, and causing pancreatic insulin release. These effects are demonstrated clinically as reduced appetite and weight loss, decreased insulin resistance, and improved postprandial blood glucose.
The U.S. Food and Drug Administration has approved exenatide for patients with type 2 diabetes who are taking sulfonylureas and/or metformin but are suboptimally controlled. In clinical studies with patients taking metformin, sulfonylureas, or both, addition of 10 µg twice daily of exenatide improved glycated hemoglobin (A1C) by 0.8%, 0.9%, and 0.8% and reduced weight by 2.8 kg (6.2 lb), 1.9 kg (4.2 lb), and 1.6 kg (3.5 lb), respectively, over 30 weeks compared with the addition of placebo.1–3 Cumulatively, the change in 2-hour postprandial glucose concentration following administration of exenatide at week 30 compared with baseline was –63 mg/dl for 5 µg BID and –71 mg/dl for 10 µg BID, compared with +11 mg/dl for placebo. This reduction may be most important if limiting postprandial glucose excursion is to be considered a priority.
Because thiazolidinedione (TZD) therapy and insulin therapy often are associated with weight gain, exenatide may be a better addition to oral therapy in overweight or obese patients. Exenatide is appropriate only for patients who are able to sense hypoglycemia, have adequate renal function (CrCl >30), and do not have gastroparesis. Exenatide requires near-constant refrigeration, so it may be necessary to avoid in patients unwilling or unable to make necessary provisions.
Nausea is common with exenatide use, and it seems important to remind patients to cease eating when they become full to prevent further nausea. Many patients have been raised to "finish your plate," but this can promote discomfort and nausea. Also, timing can affect nausea, with some people finding it easier to dose right before the meal and others finding that taking the medication 20–30 minutes prior to eating is tolerable. Dosing much longer than that before a meal can cause increased nausea in some patients. Usually, 1 month of 5-µg therapy twice daily is adequate before titrating to 10 µg, but some patients require longer or shorter therapy depending on their nausea and glucose response.
The effects of exenatide's use in those who are diet-controlled, considered to have pre-diabetes, or using insulin have not been established. However, two abstracts from this year's American Diabetes Association Scientific Sessions outlined use of exenatide in insulin users. In one, 17 type 2 insulin users took exenatide for 3 months and had a 0.76% reduction in A1C and 40.8% reduction in insulin dose. Almost 18% of the subjects discontinued insulin.4 In another study, 41 type 2 patients were given 5 µg exenatide twice daily for 8 weeks, resulting in 0.9% reduction in A1C and significantly decreased mean doses of insulin.5 These effects on A1C are similar to those seen using exenatide with sulfonylureas and metformin.
While use with TZDs, insulin, and monotherapy remains off-label, exenatide's application for these patients may eventually prove to be useful, and with the possibility for further potential applications, its patient population could continue to expand.
Footnotes
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References
2. Defronzo RA, Ratner RE, Han J, et al.: Effects of exenatide
(exendin-4) on glycemic control and weight over 30 weeks in metformin-treated
patients with type 2 diabetes. Diabetes Care 28: 1092–1100, 2005.
3. Kendall DM, Riddle MC, Rosenstock J, et al.: Effects of exenatide
(exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes
treated with metformin and a sulfonylurea. Diabetes
Care 28:1083–1091, 2005.
4. Oyer DS, Crawford RS, Shah A, et al.: Exenatide in diabetic patients on insulin and TZDs (Abstract). Diabetes 55 (Suppl. 1):A471 –A472, 2006.
5. Bhatia R, Viswanathan P, Chaudhuri A, et al.: Exenatide causes weight loss and a reduction in the insulin dose along with an improvement in HbA1c in obese type 2 diabetics on insulin (Abstract). Diabetes 55 (Suppl. 1): A105, 2006.
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